Premium
Ratio of serum γ‐GT/ALT rather than ISDR variability is predictive for initial virological response to IFN‐α in chronic HCV infection
Author(s) -
Mihm Sabine,
Monazahian Masyar,
Grethe Stefanie,
Fechner Charlotte,
Ramadori Giuliano,
Thomssen Reiner
Publication year - 1999
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/(sici)1096-9071(199907)58:3<227::aid-jmv7>3.0.co;2-7
Subject(s) - virology , hepatitis c virus , alanine transaminase , interferon , virus , predictive value , viral load , flaviviridae , viral disease , biology , medicine , immunology
Chronic hepatitis C virus (HCV) infection in humans is treated at present with interferon (IFN)‐α. Because the proportion of patients responding to therapy with sustained or even just with transient elimination of viral RNA is low, several potential prognostic parameters have been evaluated to predict the outcome of the therapy. The present study aimed to prove the validity of a predictive parameter described previously for initial virological response, namely the ratio of serum γ‐glutamyltransferase/alanine transaminase (γ‐GT/ALT) activity in connection with virus genotypes 1a, 1b, and 3a, prospectively and to compare the predictive value of these combined parameters with amino acid variability within the interferon sensitivity determining region (ISDR). The prospective analysis confirmed previous data on the predictive value of the serum γ‐GT/ALT ratio. Concerning ISDR variability, the majority of ISDR sequences obtained from the mostly nonresponding type 1b‐infected individuals (23/28) resembled nonmutant types (27/28). Isolates from type 3a‐infected patients responding to therapy in the majority of cases (13/20) exclusively resembled nonmutant types when compared with databank type 3a sequences, but were mutant when compared with the prototype sequence HCV‐J. However, the initial virological responsiveness among both type 1b‐ and type 3a‐infected patients did not correlate to ISDR variability. In contrast, virological responsiveness was closely related to serum γ‐GT/ALT ratio. The data are not necessarily contrary to the concept that the number of amino acid exchanges within the ISDR compared with the prototype HCV‐J sequence is related to some extent to IFN‐α sensitivity. The ratio of serum γ‐GT/ALT in combination with HCV genotype, however, was found to be a more reliable and stringent predictive parameter. J. Med. Virol. 58:227–234, 1999. © 1999 Wiley‐Liss, Inc.